Propofol Withdrawal Dyskinesia in a Parkinson’s Disease Patient with Levodopa-Induced Dyskinesia

The precise mechanism of dyskinesia in Parkinson ’ s disease (PD) remains unclear. Herein, we report a case of a patient with PD who and propofol as premedication before deep brain stimulation (DBS) surgery. We also discuss the mechanisms underlying PD dyskinesia.

dyskinesia after a bolus injection of propofol, and increasing the dose worsened the dyskinesia. Another patient also developed dyskinesia after starting continuous intravenous infusion of propofol, which did not resolve even after stopping the propofol infusion. In these cases, dyskinesia occurred at high concentrations of propofol in the plasma. This phenomenon is similar to levodopa-induced peak-dose dyskinesia, which occurs when the levodopa plasma levels are the highest. However, in our case, dyskinesia appeared not during propofol infusion but several minutes after cessation of propofol infusion; it was followed by the appearance of a PD symptom typically observed in the "off" state, i.e., resting tremor. Phenomenologically, the dyskinesia of our patient was very similar (i.e., predominant in lower legs, ballistic movement) to levodopainduced end-of-dose dyskinesia. Although the blood levels of propofol were not measured in this case, we speculated that little amount of propofol remained in the patient's system when the dyskinesia appeared, since the half-life of the blood concentration of propofol is 2-4 min. 1 Therefore, we surmised the patient had propofol-induced end-of-dose dyskinesia. Previous patients with propofol-induced dyskinesia had a history of preoperative levodopa-induced peak-dose dyskinesia, whereas our patient had preoperative levodopa-induced end-of-dose dyskinesia. The degree of functional changes in direct and indirect pathways in the cortico-basal ganglia circuit was theorized to differ between peak and diphasic (levodopa-induced end-of-dose and/or initialdose) dyskinesia. 4 Considering the literature and our observations, once functional changes of cortico-basal ganglia circuits, which depend on the type of dyskinesia in each case, are established, dyskinesia can be triggered by either dopamine or propofol. One study showed that intravenous injection of propofol increases dopamine concentration in the sensory cortex of rats. 5 This phenomenon may explain the mechanisms of both propofol-induced peak-dose and end-of-dose dyskinesia in patients with advanced PD. However, considering that not all patients with dyskinetic PD show propofol-induced dyskinesia, and propofol's effect on dopamine release is controversial, 6 mechanisms of dyskinesia appearance seem to differ between dopamine and propofol induction.
There are two main neurotransmitters in the cortico-basal ganglia circuits: gamma-aminobutyric acid (GABA) and glutamate. Several reports have shown how propofol enhanced GABAergic synaptic transmission 7 and its inhibitory effect on glutamate release. Further, altered amounts of both GABA 8 and glutamate receptors in advanced PD have been reported. Previous reports suggest that the functional changes of the GABAergic-glutamatergic system may play an important role in peak dose propofolinduced dyskinesia in PD. 3 Therefore, these neurotransmitters may also be implicated in the pathophysiology of propofolinduced end-of-dose dyskinesia in PD. Altered cholinergic signaling has been shown to be another important factor in the development of dyskinesia. Drugs targeting various types of nicotine acetylcholine receptors as well as muscarine acetylcholine receptors are thought to be effective interventions to alleviate dyskinesia. 9 Some of these receptors are expressed in GABA interneurons and glutamatergic terminals. Therefore, considering the effects of propofol on the GABAergic-glutamatergic system, withdrawal of anticholinergic medication may play a role in propofol-induced dyskinesia. These speculations may help to elucidate the mechanisms of both levodopa-induced peak-dose and end-of-dose dyskinesia in PD. Further research is warranted to pursue this hypothesis. Conflicts of Interest. All authors have no conflicts of interest to declare that are relevant to the content of this article.
Availability of Data and Material. All data generated or analyzed during this study are included in this published article and its supplementary information files.
Author Contributions. A.N. and Y.S. made substantial contributions to the study concept and design, acquisition of the data, and manuscript for intellectual content. H.I., J.T., and M.O. participated in drafting the article or critically revising it for important intellectual content. All authors gave final approval of the version to be submitted and any revised version.
Ethics Approval. All procedures performed in this study were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration.
Consent for Participate. Informed consent was obtained from the patient included in the case report.
Consent for Publication. The patient gave written informed consent for the publication of any potentially identifiable images or data included in this article.